Using positron emission scanning and brain MRI, neuroanatomical correlates of hunger and satiety have been investigated. Importantly, recent analyses of this collected data has indicated that the left dorsolateral prefrontal cortex, an area of the brain important in reward processing, may be a satiety center. Neuronal activation in the left dorsolateral prefrontal cortex following a meal is consistently lower in this area in obese versus lean individuals, in both men and women. Furthermore, in individuals who have lost weight, neuronal activation is closer to that of lean, and higher than in obese individuals. In subjects with Prader-Willi syndrome, a monogenic form of obesity characterized by extreme hyperphagia, neuronal activity following a meal actually decreases, and is significantly different compared to controls matched for adiposity. Post-prandial glucagons like-peptide-1 response is also positively associated with neuronal activity in this same brain region. Further analyses using a region of interest approach to analyze activity across the entire brain region (rather than a voxel based approach) localizes the lower activity following a meal to the left dorsolateral prefrontal cortex (and more specifically to the left middle and inferior gyri) consistent with our previous results. To investigate the effect of stimulation of the left dorsolateral prefrontal cortex on food intake, a randomized study using trans-cranial direct current stimulation (TDCS) was designed. Obese volunteers will be randomized to TDCS versus sham therapy. Volunteers will receive treatment 3 days in a row as inpatients on the clinical research unit, while eating ad-libitum from computerized vending machines. Volunteers will then be additionally randomized to behavioral weight loss intervention versus standard dietary instruction. Volunteers will continue to receive TDCS for an additional 4 weeks to investigate the effects of this treatment on weight loss. Whether behavioral therapy has an additive effect on top of TDCS will also be investigated. Recruitment is currently ongoing for this protocol
